Oligohydramnios, renal insufficiency, and ileal perforation in preterm infants after intrauterine exposure to indomethacin

Vanhaesebrouck, Piet; Thiery, M; Leroy, Jules; Govaert, Paul; Praeter, Claudine De; Coppens, Marc; Cuvelier, C; Dhont, Marc

doi:10.1016/s0022-3476(88)80392-5

Cited by 85 publications

(9 citation statements)

References 34 publications

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“…32 Furthermore, gastrointestinal adverse reactions have been observed among preterm and term infants whose mothers were treated with antenatal indomethacin without direct contact of the nonsteroidal anti-inflammatory drugs with the gastrointestinal tract of the newborn. [35][36][37] Serum creatinine levels in our patients were within normal range at all times, so there was no contraindication for a second or third dose of ibuprofen when it was needed. This might be an explanation for the higher rate of pharmacologic ductal closure observed in our study.…”

Section: Discussionmentioning

confidence: 77%

Closure of Patent Ductus Arteriosus With Oral Ibuprofen Suspension in Premature Newborns: A Pilot Study

et al. 2003

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ABSTRACT. Objective. Patent ductus arteriosus (PDA), a common finding among premature infants, is conventionally treated by intravenous indomethacin. Intravenous ibuprofen was recently shown to be as effective and to have fewer adverse reactions in preterm infants. If equally effective, then oral ibuprofen for PDA closure would have several important advantages over the intravenous route. This study was designed to determine whether oral ibuprofen treatment is efficacious and safe in closure of a PDA in premature infants with respiratory distress syndrome.Methods. Twenty-two preterm newborns (gestational age: 27.5 ؎ 1.75 [range: 23.9 -31 weeks]; weight: 979 ؎ 266 [range: 380-1500 g]) with PDA and respiratory distress syndrome were studied prospectively. They received oral ibuprofen suspension 10 mg/kg/body weight for the first dose, followed at 24-hour intervals by 2 additional doses of 5 mg/kg each, if needed, starting on the second day of life. Echocardiography was performed before treatment and 24 hours after each dose. Every child underwent cranial ultrasonography before and after each ibuprofen dose. The rate of ductal closure, the need for additional treatment, side effects, complications, and the infants' clinical courses were recorded.Results. Ductal closure was achieved in all newborns except for 1 (95.5%), in whom clinically nonsignificant ductal shunting persisted. No infant required surgical ligation of the ductus. There was no reopening of the ductus after closure had been achieved. Fourteen newborns were treated with 1 dose of ibuprofen, 6 were treated with 2 doses, and the remaining 2 were treated with 3 doses. The survival rate at 1 month was 86.4% (19 of 22). Three (13.6%) infants died from the following causes: 1 who was born at 24 weeks' gestation with a birth weight of 380 g died as a result of extreme prematurity complications, necrotizing enterocolitis, and low birth weight; 1 died as a result of Candida sepsis; and the third died as a result of Klebsiella sepsis. Intraventricular hemorrhage was observed in 7 infants. The classification was changed from grade 2 to grade 3 in 1 and from grade 0 to grade 1 or higher in 3 others. The rate of survival to discharge was 86.4% (19 of 22). No bronchopulmonary dysplasia was observed in the study group, and there was no case of tendency to bleed. There were no significant differences in the levels of serum creatinine before and after treatment with oral ibuprofen.Conclusions. Oral ibuprofen suspension may be an effective and safe alternative for PDA closure in premature infants with PDA. However, larger comparative studies are warranted. Pediatrics 2003;112:e354 -e358. URL: http://www.pediatrics.org/cgi/content/full/112/5/ e354; oral ibuprofen, patent ductus arteriosus, premature newborns.ABBREVIATIONS. PDA, patent ductus arteriosus; RDS, respiratory distress syndrome; IVH, intraventricular hemorrhage; NEC, necrotizing enterocolitis.T he incidence of patent ductus arteriosus (PDA) in premature infants who weigh between 500 and 1500 g at birth is appr...

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Section: Discussionmentioning

confidence: 77%

Closure of Patent Ductus Arteriosus With Oral Ibuprofen Suspension in Premature Newborns: A Pilot Study

et al. 2003

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“…This holds also for short-term exposure in the human neonate. Some case reports show that prolonged prenatal use of indomethacin can lead to deleterious renal and extrarenal effects (8,9,(24)(25)(26), whereas other reports could not detect any serious side effects (10,27).…”

Section: Resultsmentioning

confidence: 99%

Effects of Prenatal Exposure to Betamethasone and Indomethacin on the Glomerular Filtration Rate in the Preterm Infant

et al. 1994

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“…Indomethacin is administered to pregnant women to try and prevent preterm delivery. Adverse effects of indomethacin on the fetus and neonate have been described including oligohydramnios, persistent renal insufficiency, gastrointestinal bleeding and perforation, and persistent pulmonary hypertension (22)(23)(24)(25)(26). However, it has not been determined whether there is any effect on fetal glomerular development following exposure to intrauterine indomethacin.…”

Section: Discussionmentioning

confidence: 99%

Renal Glomeruli and Tubular Injury Following Indomethacin, Ibuprofen, and Gentamicin Exposure in a Neonatal Rat Model

et al. 2007

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Indomethacin, ibuprofen, and gentamicin are commonly administered to neonates between 24 and 28 wk gestation when glomerulogenesis is still occurring. Indomethacin is known to cause renal failure in up to 25% of infants treated. Possible morphologic effects of these drugs are largely unknown. The purpose of this study was to determine the type of renal changes found on light (LM) and electron microscopy (EM) following administration of indomethacin, ibuprofen, and gentamicin in a neonatal rat model. Rat pups were exposed to indomethacin or ibuprofen and/or gentamicin antenatally for 5 d before birth or postnatally for 5 d from d 1 of life. Pups were killed at 14 d of age. LM examination in all indomethacin-and ibuprofen-treated pups both antenatally and postnatally showed vacuolization of the epithelial proximal tubules, interstitial edema, intratubular protein deposition but no significant glomerular changes. EM examination showed pleomorphic mitochondria and loss of microvilli in the tubules. The glomeruli showed extensive foot process effacement and irregularities of the glomerular basement membrane. EM changes were most marked in pups treated antenatally with ibuprofen, and indomethacin with gentamicin postnatally. Indomethacin, ibuprofen, and gentamicin cause significant change in glomerular and tubular structure in the neonatal rat model. U p to 5% of infants are delivered between 24 and 28 wk gestation, at a time when glomerulogenesis is occurring. Indomethacin and ibuprofen are commonly used in extremely premature neonates to close a patent ductus arteriosus at this time (1,2). Both of these drugs are successful in closing the ductus (3,4), but the morphologic effects these drugs may have on the developing kidney are unknown. Both drugs are known to be nephrotoxic, with indomethacin causing acute renal failure in 25% of premature neonates treated (5). Ibuprofen is considered to have less renal toxicity than indomethacin, but is as efficacious as indomethacin at closing the patent ductus (6). Two animal studies have shown an effect on glomerulogenesis by ibuprofen and a COX-2 selective inhibitor. In both studies, the number and size of glomeruli was decreased (7,8).Gentamicin is frequently administered at the same time as indomethacin or ibuprofen. Gentamicin has been shown in in vitro studies to affect nephron development (9). The combination of nonsteroidal anti-inflammatory drugs (NSAID) and gentamicin on glomerular development is unknown. The renal effect of indomethacin has not been examined in a neonatal animal model, nor has the combination of both indomethacin or ibuprofen and gentamicin.In the human, glomerulogenesis is complete at 36 wk gestation. The metanephron develops at 5 wk gestation, with vesicular glomeruli development occurring at 18 wk gestation. Glomerular tubular development occurs from 24 wk gestation and is complete at 36 wk (10 -12). In the rat model, glomerulogenesis continues after birth until 14 d of life (13). At birth the neonatal rat kidney is similar to that of a ...

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Oligohydramnios, renal insufficiency, and ileal perforation in preterm infants after intrauterine exposure to indomethacin

Cited by 85 publications

References 34 publications

Closure of Patent Ductus Arteriosus With Oral Ibuprofen Suspension in Premature Newborns: A Pilot Study

Closure of Patent Ductus Arteriosus With Oral Ibuprofen Suspension in Premature Newborns: A Pilot Study

Effects of Prenatal Exposure to Betamethasone and Indomethacin on the Glomerular Filtration Rate in the Preterm Infant

Renal Glomeruli and Tubular Injury Following Indomethacin, Ibuprofen, and Gentamicin Exposure in a Neonatal Rat Model

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